Journal of pharmaceutical sciences最新文献_第7页

Quercetin/Polyethyleneimine Modified Gold Nanoconjugates Inhibit Apoptosis and ROS Production Induced by Hydrogen Peroxide in DRG Sensory Neurons 槲皮素/聚乙烯亚胺修饰金纳米共轭物抑制过氧化氢诱导的 DRG 感觉神经元凋亡和 ROS 生成

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-01 DOI: 10.1016/j.xphs.2024.08.008

{"title":"Quercetin/Polyethyleneimine Modified Gold Nanoconjugates Inhibit Apoptosis and ROS Production Induced by Hydrogen Peroxide in DRG Sensory Neurons","authors":"","doi":"10.1016/j.xphs.2024.08.008","DOIUrl":"10.1016/j.xphs.2024.08.008","url":null,"abstract":"<div><div>The basis of most neurological syndromes is the accumulation of free radical molecules. Quercetin is a polyphenolic bioflavonoid molecule and it has a very strong antioxidant effect by maintaining oxidative balance. There are many difficulties in the clinical use of quercetin due to its hydrophobic structure, low solubility, instability, poor oral bioavailability, and limited tissue-barrier penetration. Its synergistic use in complex with gold nanoparticles (AuNPs) could overcome these problems. AuNPs have recently emerged as an attractive candidate for delivery applications of various biomolecules and drugs. The aim of this study was to synthesize two different sized gold nanoparticles (AuNP<sub>20</sub> and AuNP<sub>50</sub>) modified with polyethyleneimine (PEI) and quercetin, evaluate their potential neuroprotective effects on the in vitro oxidative stress model using DRG primary sensory neurons. It was shown that the antioxidant and anti-apoptotic ability of the bioflavonoid was preserved after exposure to the designed quercetin modified AuNPs. The PEI surface coating increased the stability and biocompatibility of the AuNPs in both sizes. It also potentially enables additional surface functionalization. This study indicates that designed nanoparticles (AuNP-Q-PEI) with different sizes could be a useful potential platform for the treatment of neurodegenerative syndromes or cancer diseases.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Advisory Board 编辑顾问委员会

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-01 DOI: 10.1016/S0022-3549(24)00383-6

引用次数: 0

Past, Current, and Future: Application of Image Analysis in Small Molecule Pharmaceutical Development 过去、现在和未来：图像分析在小分子药物开发中的应用。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-01 DOI: 10.1016/j.xphs.2024.08.003

{"title":"Past, Current, and Future: Application of Image Analysis in Small Molecule Pharmaceutical Development","authors":"","doi":"10.1016/j.xphs.2024.08.003","DOIUrl":"10.1016/j.xphs.2024.08.003","url":null,"abstract":"<div><div>The often-perceived limitations of image analysis have for many years impeded the widespread application of such systems as first line characterisation tools. Image analysis has, however, undergone a notable resurgence in the pharmaceutical industry fuelled by developments system capabilities and the desire of scientists to characterize the morphological nature of their particles more adequately. The importance of particle shape as well as size is now widely acknowledged.</div><div>With the increasing use of modelling and simulations, and ongoing developments though the integration of machine learning and artificial intelligence, the utility of image analysis is increasing significantly driven by the richness of the data obtained. Such datasets provide means to circumvent the requirement to rely on less informative descriptors and enable the move towards the use of whole distributions. Combining the improved particle size and shape measurement and description with advances in modelling and simulations is enabling improved means to elucidate the link between particle and bulk powder properties.</div><div>In addition to improved capabilities to describe input materials, approaches to characterize single components within multicomponent systems are providing scientists means to understand how their material may change during manufacture thus providing a means to link the behaviour of final dosage forms with the particle properties at the point of action.</div><div>The aim is to provide an overview of image analysis and update readers with innovations and capabilities to other methods in the small molecule arena. We will also describe the use of AI for the improved analysis using image analysis.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-field NMR Works as a Rapid, Automatic, Non-Invasive and Wide-Scale Coverage Technique for Aggregates Indication in Biomacromolecule Development 低场核磁共振是一种快速、自动、无创和大范围覆盖的技术，可用于生物大分子开发过程中的聚集体指示。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-01 DOI: 10.1016/j.xphs.2024.07.021

{"title":"Low-field NMR Works as a Rapid, Automatic, Non-Invasive and Wide-Scale Coverage Technique for Aggregates Indication in Biomacromolecule Development","authors":"","doi":"10.1016/j.xphs.2024.07.021","DOIUrl":"10.1016/j.xphs.2024.07.021","url":null,"abstract":"<div><div>Protein aggregation is challenging for biopharmaceutical drug, because it affects the stability of protein formulations in real-time. However, current techniques for protein aggregate indication meet a number of limitations including limited aggregate size range, complex pre-treatments and lack of chromatographic approaches. Herein, a rapid, automatic, non-invasive and wide-scale coverage technique for aggregates indication is developed to overcome these challenges. Firstly, the response of low-field nuclear magnetic resonance (LF-NMR) to the aggregates is explored by making a comparison with certain established techniques. LF-NMR achieves a high sensitivity of water proton transverse relaxation rate (R<sub>2</sub> of H<sub>2</sub>O, hereinafter referred as R<sub>2</sub>(H<sub>2</sub>O)) to protein aggregates from nanometer to micrometer. Then, the quantitative relationship between R<sub>2</sub>(H<sub>2</sub>O) and aggregates is investigated furtherly. R<sub>2</sub>(H<sub>2</sub>O) could serve as an all-size coverage protein aggregates indicator during development. As a non-invasive method, LF-NMR does not need any sample handling. It takes only 44 s for one test, and saves a lot of manpower, materials and costs. Compared with other established analytical techniques, the technique developed here could be a powerful tool for a rapid, automatic, non-invasive and wide-scale coverage technique for aggregates indication in biomacromolecule development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analytical Procedure Development and Proposed Established Conditions: A Case Study of a Mass Spectrometry Based NDSRI Analytical Procedure 分析程序的开发和拟议的既定条件：基于质谱法的 NDSRI 分析程序案例研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-01 DOI: 10.1016/j.xphs.2024.07.022

{"title":"Analytical Procedure Development and Proposed Established Conditions: A Case Study of a Mass Spectrometry Based NDSRI Analytical Procedure","authors":"","doi":"10.1016/j.xphs.2024.07.022","DOIUrl":"10.1016/j.xphs.2024.07.022","url":null,"abstract":"<div><div>With the finalization of the ICH Q14 Analytical Procedure Development guideline, how to apply enhanced approaches (such as analytical quality by design (AQbD)) to develop an analytical procedure, and to propose Established Conditions (ECs) and corresponding reporting categories, is increasingly being discussed. To gain practical experience in applying an enhanced approach for method development and identifying ECs, we developed, validated, and implemented an analytical procedure for a nitrosamine drug substance-related impurity (NDSRI). Here, as an example of the application of Q12 Lifecycle Management guideline principles in regards to analytical procedures, we briefly elaborate how: 1) the principles documented in the ICH Q14 guideline for analytical procedure development were applied, with the focus on identifying an Analytical Target Profile (ATP), knowledge management and risk assessment; 2) analytical procedure robustness according to the recommendations in ICH Q2(R2) Validation of Analytical Procedure guideline and Q14, were evaluated; and 3) mass spectrometry ECs and associated proposed reporting categories were proposed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations. 表面成分和润湿性对高载药量无定形分散制剂溶解性能的重要性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-09-28 DOI: 10.1016/j.xphs.2024.09.020

Tze Ning Hiew, Marina A Solomos, Prapti Kafle, Hector Polyzois, Dmitry Y Zemlyanov, Ashish Punia, Daniel Smith, Luke Schenck, Lynne S Taylor

{"title":"The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations.","authors":"Tze Ning Hiew, Marina A Solomos, Prapti Kafle, Hector Polyzois, Dmitry Y Zemlyanov, Ashish Punia, Daniel Smith, Luke Schenck, Lynne S Taylor","doi":"10.1016/j.xphs.2024.09.020","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.020","url":null,"abstract":"<p><p>One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. Hydrophobic drugs have poor wettability and require a substantial amount of polymer to stabilize the amorphous drug and facilitate release. Using grazoprevir and hypromellose acetate succinate as model drug and polymer respectively, the interplay between particle surface composition, particle wettability, and release performance was investigated. A hierarchical particle approach was used where the surfaces of high drug loading ASDs generated by either solvent evaporation or co-precipitation were further modified with a secondary excipient (i.e., polymer or wetting agent). The surface-modified particles were characterized for drug release, wettability, morphology, and surface composition using two-stage dissolution studies, contact angle measurements, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. Despite surface modification with hydrophilic polymers, hierarchical cPAD particles did not consistently exhibit good release performance. Contact angle measurements showed that the secondary excipient had a profound impact on particle wettability. Particles with good wettability showed improved drug release relative to particles that did not wet well, even with similar drug loadings. These observations underscore the intricate interplay between particle wettability and performance in amorphous dispersion formulations and illustrate a promising hierarchical particle approach to formulate high drug loading amorphous dispersions with improved dissolution performance.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study of polymer component migrated in medicinal product from transportation packaging component: A systematic assessment beyond regulatory expectations. 运输包装部件迁移到医药产品中的聚合物成分研究：超越监管期望的系统性评估。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-09-28 DOI: 10.1016/j.xphs.2024.09.021

Sandeep Zokande, Kavita Inamdar, Amit Gosar, Amit Kale

{"title":"Study of polymer component migrated in medicinal product from transportation packaging component: A systematic assessment beyond regulatory expectations.","authors":"Sandeep Zokande, Kavita Inamdar, Amit Gosar, Amit Kale","doi":"10.1016/j.xphs.2024.09.021","DOIUrl":"10.1016/j.xphs.2024.09.021","url":null,"abstract":"<p><p>Light Density Polyethylene (LDPE) bottles with a specific resin were chosen as container closure system (CCS) to fill \"Latanoprost ophthalmic solution\" (a generic drug product). As an alternative packaging component, additional manufacturer of LDPE bottles with the same characteristics as the previously selected LDPE bottles was chosen. The appropriateness of both packaging components was evaluated using an extractables and leachable (E&L) study and a formal stability programme that monitored quality of latanoprost ophthalmic solution. The results of relevant quality attributes in stability samples of latanoprost ophthalmic solution packed in both LDPE bottles were compared. It noticed that an unknown impurity in latanoprost ophthalmic solution packaged in LDPE bottles manufactured by an additional manufacturer. Further study revealed that this unknown impurity is Epsilon-caprolactam, a leachable of plastic used in the transportation of LDPE bottles. The leachability was validated through an extraction analysis of a plastic bag used for transportation. Thus, in certain cases, when the source of leachable is not identifiable by an E&L examination of primary, secondary, and tertiary packaging components, the assessment could be extended to include packaging components utilized throughout the supply chain.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Review of machine learning for lipid nanoparticle formulation and process development. 脂质纳米颗粒配方和工艺开发的机器学习回顾。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-09-27 DOI: 10.1016/j.xphs.2024.09.015

Phillip J Dorsey, Christina L Lau, Ti-Chiun Chang, Peter C Doerschuk, Suzanne M D'Addio

{"title":"Review of machine learning for lipid nanoparticle formulation and process development.","authors":"Phillip J Dorsey, Christina L Lau, Ti-Chiun Chang, Peter C Doerschuk, Suzanne M D'Addio","doi":"10.1016/j.xphs.2024.09.015","DOIUrl":"10.1016/j.xphs.2024.09.015","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) are a subset of pharmaceutical nanoparticulate formulations designed to encapsulate, stabilize, and deliver nucleic acid cargoes in vivo. Applications for LNPs include new interventions for genetic disorders, novel classes of vaccines, and alternate modes of intracellular delivery for therapeutic proteins. In the pharmaceutical industry, establishing a robust formulation and process to achieve target product performance is a critical component of drug development. Fundamental understanding of the processes for making LNPs and their interactions with biological systems have advanced considerably in the wake of the COVID-19 pandemic. Nevertheless, LNP formulation research remains largely empirical and resource intensive due to the multitude of input parameters and the complex physical phenomena that govern the processes of nanoparticle precipitation, self-assembly, structure evolution, and stability. Increasingly, artificial intelligence and machine learning (AI/ML) are being applied to improve the efficiency of research activities through in silico models and predictions, and to drive deeper fundamental understanding of experimental inputs to functional outputs. This review will identify current challenges and opportunities in the development of robust LNP formulations of nucleic acids, review studies that apply machine learning methods to experimental datasets, and provide discussion on associated data science challenges to facilitate collaboration between formulation and data scientists, aiming to accelerate the advancement of AI/ML applied to LNP formulation and process optimization.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stability modeling methodologies to enable earlier patient access. 稳定性建模方法，让患者更早获得治疗。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-09-27 DOI: 10.1016/j.xphs.2024.09.018

Andrew Lennard, Boris Zimmermann, Didier Clenet, Michael Molony, Cecilia Tami, Cristian Oliva Aviles, Amy Moran, Philip Pue-Gilchrist, E'Lissa Flores

{"title":"Stability modeling methodologies to enable earlier patient access.","authors":"Andrew Lennard, Boris Zimmermann, Didier Clenet, Michael Molony, Cecilia Tami, Cristian Oliva Aviles, Amy Moran, Philip Pue-Gilchrist, E'Lissa Flores","doi":"10.1016/j.xphs.2024.09.018","DOIUrl":"10.1016/j.xphs.2024.09.018","url":null,"abstract":"<p><p>Over recent years, confidence has been gained that predictive stability modeling approaches using statistical tools, prior knowledge and industry experience enable, in many instances, a robust and reliable shelf-life/expiry or retest period prediction for medicinal products. These science and risk-based approaches can compensate for not having a complete real-time stability data set to be included in regulatory applications at the time of initial submission and, thereby, accelerate the availability of new medicines. Examples of predictive stability modeling include accelerated stability assessment procedure (ASAP), advanced kinetic modeling (AKM), and novel modeling approaches that involve the use of Bayesian statistics and Artificial Intelligence (AI) applications such as Machine Learning (ML), with applicability to both synthetic and biological molecules. For biologics, product-specific and platform prior knowledge could be used to overcome model limitations known for non-quantitative stability indicating attributes. A successful ongoing verification approach by comparing the predicted data with real-time stability data would be an appropriate risk management approach which is intended to address regulatory concerns, and further build confidence in the robustness of these predictive modelling approaches with regulatory agencies. Global regulatory acceptance of stability modeling could allow patients to receive potential life-saving medications faster without compromising quality, safety or efficacy.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses. 利用预测性先天性免疫反应评估腺相关病毒载体空壳的免疫原性风险。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-09-24 DOI: 10.1016/j.xphs.2024.09.006

Nicole Jarvi, Kirk Hofman, Aditi Venkatesh, Emily Gorecki, Sathy V Balu-Iyer

{"title":"Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.","authors":"Nicole Jarvi, Kirk Hofman, Aditi Venkatesh, Emily Gorecki, Sathy V Balu-Iyer","doi":"10.1016/j.xphs.2024.09.006","DOIUrl":"10.1016/j.xphs.2024.09.006","url":null,"abstract":"<p><p>Immunogenicity of gene therapy and the impacts on safety and efficacy are of increasing interest in the pharmaceutical industry. Unique structural aspects of gene therapy delivery vectors, such as adeno-associated viral (AAV) vectors, are expected to activate the innate immune system. The risk of innate immune activation is critical to understand due to the potential impacts on safety and on subsequent adaptive immune responses. In this study, we investigated the responses of key innate immune players-dendritic cells, natural killer (NK) cells, and the complement system-to AAV8 capsids. Immunogenicity risk was also predicted in the presence empty AAV capsids for AAV gene therapy. Compared to genome-containing \"full\" AAV8 capsids, empty AAV8 capsids more strongly induced proinflammatory cytokine production and migration by human and mouse dendritic cells, but the \"full\" capsid increased expression of co-stimulatory markers. Furthermore, in an NK cell degranulation assay, we found mixtures of empty and full AAV8 capsids to activate expression of TNF-α, IFN-γ, and CD107a more strongly in multiple NK cell populations compared to either capsid type alone. Serum complement C3a was also induced more strongly in the presence of mixed empty and full AAV8 capsid formulations. Risk for innate immune activation suggests the importance to determine acceptable limits of empty capsids. Immunogenicity risk assessment of novel biological modalities will benefit from the aforementioned in vitro innate immune activation assays providing valuable mechanistic information.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0